Project Summary Countries in the Greater Mekong Subregion (GMS) have together declared commitment to eliminate malaria by 2030. Plasmodium vivax represents a key challenge for this goal. This parasite is now the predominant species of malaria in the region. Able to lie dormant in the human liver as hypnozoites, the parasite can cause multiple episodes of malaria from a single infectious mosquito bite. Hypnozoites can persist for months to years without causing any symptoms; they represent the parasite reservoir that requires particular attention if malaria elimination is to be accelerated. Without biological markers to identify hypnozoite infection, mass administration of primaquine is the only way to quickly remove this latent form of parasites from the population. The Ministries of Public Health (MOPH) of Thailand and Myanmar are considering integrating mass primaquine preventive treatment (MPPT) into their national malaria programs. Evidence-based decision making is crucial and will require evaluation of effectiveness and financial feasibility. In this study, we will work with Thai and Myanmar MOPH to conduct a cluster-randomized trial of MPPT. In the first phase (years 1-2), we will conduct the study in a small population of 3,000 to evaluate safety, effectiveness, and feasibility to scale up for the next phase. In the second phase (years 3-5), the population size will be expanded to >100,000 using a stepped wedge design to provide statistically robust evaluation of MPPT. Multiple integrated approaches will be employed including malaria passive case detection, mass blood survey, molecular parasite detection and genotyping, vector surveys, G6PD screening and genotyping, and cost-effectiveness analysis. By working closely with the public sectors at both local and central levels, we will be able to not only provide scientifically rigorous data to inform policy makers, but also improve local staff capacities through collaborative activities. Assuming sufficient benefits and acceptable risks and costs, this study will lay down the framework for MPPT implementation at the national level.